We have cloned and characterized two mitogen-inducible genes from human peripheral blood T cells that comprise members of the NF-(kappa)B family of transcription factors. Biochemical studies previously have defined NF-(kappa)B as a heterodimer of 50 kD (p5O) and 65 kD (p65). We have shown that pAT 243 encodes a 105 kD precursor protein for p5O that becomes processed, resulting in an amino terminal 50 kD protein that shows binding activity to an NF-(kappa)B binding site, either as a homodimer or a heterodimer with p65. The amino-terminal domain has regions homologous to the oncogene rel. The carboxy-terminal domain contains repeat structures that are found in a variety of proteins and that probably determine protein-protein interactions. We have characterized an additional gene, pAT 189, that resembles the structural organization of plO5 and shares 44% amino acid homology with it. Truncated 189 protein binds an NF-(kappa)B consensus sequence as a homodimer or as a heterodimer with p5O or p65. Thus, it appears that NF-(kappa)B transcription factors are unexpectedly composed of a family of polypeptides that at a minimum include p5O, pAT 189-encoded protein, c-rel, and p65.